Our proposed research has two objectives: The first objective is to find the correct mechanism for the cooperative ligand binding to proteins. This is to be achieved by extending the sequential model postulated by Koshland et al. and the allosteric transition model postulated by Monod et al. to non-equilibrium kinetic theories and by finding the time-dependent behavior of the cooperative ligand binding to hemoglobin. From our kinetic approach, we intend to resolve the apparent contradictions between the two models and to give more insight into the cooperative mechanism of the ligand binding to proteins. The cooperative ligand binding to mutant hemoglobin will also be investigated. Our second objective is to study the unwinding mechanism of DNA. As a first step toward achieving this project, we will investigate theoretical and experimental aspects of the helix-coil transition of polynucleotides induced by small ligands. We will accomplish our goal experimentally by observing the optical density change of synthetic and real DNA in the presence of formaldehyde and theoretically by means of the master equation approach. BIBLIOGRAPHIC REFERENCES: "Kinetics of Helix-Coil Transition in All Sizes of Polypeptides," T. Ree Chay and C.L. Stevens, Macromolecules 8: 531 (1975). "Model for Rupture of Base Pairing in Poly (A U) by Formaldehyde," T.R. Chay, C.L. Stevens and K-S Jhung, Biophysical Journal Abstract (20th Annual Meeting) February, 1976.